Neuroprotective effects of black soybean anthocyanins via inactivation of ASK1-JNK/p38 pathways and mobilization of cellular sialic acids

Sung Min Kim; Mi Ja Chung; Tae Joung Ha; Ha Na Choi; Seong Jae Jang; Sung Oog Kim; Myung Hoon Chun; Su Il Do; Young Kug Choo; Yong Il Park

doi:10.1016/j.lfs.2012.04.025

Neuroprotective effects of black soybean anthocyanins via inactivation of ASK1-JNK/p38 pathways and mobilization of cellular sialic acids

Sung Min Kim
, Mi Ja Chung
, Tae Joung Ha
, Ha Na Choi
, Seong Jae Jang
, Sung Oog Kim
, Myung Hoon Chun
, Su Il Do
, Young Kug Choo
, Yong Il Park

Department of Medical and Biological Sciences

The Catholic University of Korea
Rural Development Administration
Ajou University
Wonkwang University

Research output: Contribution to journal › Article › peer-review

77 Scopus citations

Abstract

Aims: To investigate neuroprotective effects of three major anthocyanins (cyanidin-3-O-glucoside, delphinidin-3-O-glucoside, and petunidin-3-O-glucoside) isolated from the black soybean (Glycine max L.) cv. Cheongja 3 seed coat against H ₂O ₂-induced cell death of human brain neuroblastoma SK-N-SH cells. Main methods: Cell viability, reactive oxygen species (ROS) generation, production and expression of heme oxygenase (HO)-1 and inactivation of mitogen-activated protein (MAP) kinase cascades were determined by MTT assay, 2,7-dichlorofluorescein diacetate (DCF-DA) assay, reverse transcriptase polymerase chain reaction (RT-PCR), and western blotting, respectively. Key findings: Pretreatment with anthocyanins reduced the cytotoxicity of H ₂O ₂ on SK-N-SH cells, dose-dependently reduced the intracellular ROS level and inactivated apoptosis signal-regulating kinase (ASK1, Thr845), p38, and c-Jun N-terminal kinase (JNK) proteins. The HO-1 and Neu1 mRNA levels were increased by H ₂O ₂ (25 μM) and further elevated by the pretreatment with anthocyanins. Sialic acids added to the culture plates not only attenuated the cytotoxicity of H ₂O ₂ (25 μM) but also reduced intracellular ROS level. These results suggest that Cheongja 3 black soybean seed coat anthocyanins have brain neuroprotective effects against oxidative stress (H ₂O ₂) by inhibiting the activation of ASK1-JNK/p38 pathways, scavenging ROS, stimulating the expression of HO-1 and, more interestingly, recruiting cellular free sialic acids through up-regulation of Neu1 sialidase gene expression. Significance: This is the first report indicating potent health benefits of black soybean seed coat anthocyanins in neuroprotection by triggering mobilization of cellular free sialic acid and utilizing it as an additional biological antioxidant in brain neural cells.

Original language	English
Pages (from-to)	874-882
Number of pages	9
Journal	Life Sciences
Volume	90
Issue number	21-22
DOIs	https://doi.org/10.1016/j.lfs.2012.04.025
State	Published - 6 Jun 2012

Bibliographical note

Funding Information:
This work was supported by a grant (No. M10619000005-07N1900-00510 ) from the Korea Science and Engineering Foundation (KOSEF) and a grant (No. PJ0071862011 ) from the Cooperative Research Program for Agriculture Science and Technology Development, Rural Development Administration , and partly by a grant from the Next-Generation BioGreen 21 Program (SSAC, PJ008109 ), Rural Development Administration, Republic of Korea.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Anthocyanins
H O
Neu1 sialidase
Oxidative stress
Sialic acid

Access to Document

10.1016/j.lfs.2012.04.025

Cite this

@article{ef53cc60ab624a2ab2b1201796d6dae9,

title = "Neuroprotective effects of black soybean anthocyanins via inactivation of ASK1-JNK/p38 pathways and mobilization of cellular sialic acids",

abstract = "Aims: To investigate neuroprotective effects of three major anthocyanins (cyanidin-3-O-glucoside, delphinidin-3-O-glucoside, and petunidin-3-O-glucoside) isolated from the black soybean (Glycine max L.) cv. Cheongja 3 seed coat against H 2O 2-induced cell death of human brain neuroblastoma SK-N-SH cells. Main methods: Cell viability, reactive oxygen species (ROS) generation, production and expression of heme oxygenase (HO)-1 and inactivation of mitogen-activated protein (MAP) kinase cascades were determined by MTT assay, 2,7-dichlorofluorescein diacetate (DCF-DA) assay, reverse transcriptase polymerase chain reaction (RT-PCR), and western blotting, respectively. Key findings: Pretreatment with anthocyanins reduced the cytotoxicity of H 2O 2 on SK-N-SH cells, dose-dependently reduced the intracellular ROS level and inactivated apoptosis signal-regulating kinase (ASK1, Thr845), p38, and c-Jun N-terminal kinase (JNK) proteins. The HO-1 and Neu1 mRNA levels were increased by H 2O 2 (25 μM) and further elevated by the pretreatment with anthocyanins. Sialic acids added to the culture plates not only attenuated the cytotoxicity of H 2O 2 (25 μM) but also reduced intracellular ROS level. These results suggest that Cheongja 3 black soybean seed coat anthocyanins have brain neuroprotective effects against oxidative stress (H 2O 2) by inhibiting the activation of ASK1-JNK/p38 pathways, scavenging ROS, stimulating the expression of HO-1 and, more interestingly, recruiting cellular free sialic acids through up-regulation of Neu1 sialidase gene expression. Significance: This is the first report indicating potent health benefits of black soybean seed coat anthocyanins in neuroprotection by triggering mobilization of cellular free sialic acid and utilizing it as an additional biological antioxidant in brain neural cells.",

keywords = "Anthocyanins, H O, Neu1 sialidase, Oxidative stress, Sialic acid",

author = "Kim, \{Sung Min\} and Chung, \{Mi Ja\} and Ha, \{Tae Joung\} and Choi, \{Ha Na\} and Jang, \{Seong Jae\} and Kim, \{Sung Oog\} and Chun, \{Myung Hoon\} and Do, \{Su Il\} and Choo, \{Young Kug\} and Park, \{Yong Il\}",

note = "Funding Information: This work was supported by a grant (No. M10619000005-07N1900-00510 ) from the Korea Science and Engineering Foundation (KOSEF) and a grant (No. PJ0071862011 ) from the Cooperative Research Program for Agriculture Science and Technology Development, Rural Development Administration , and partly by a grant from the Next-Generation BioGreen 21 Program (SSAC, PJ008109 ), Rural Development Administration, Republic of Korea.",

year = "2012",

month = jun,

day = "6",

doi = "10.1016/j.lfs.2012.04.025",

language = "English",

volume = "90",

pages = "874--882",

journal = "Life Sciences",

issn = "0024-3205",

publisher = "Elsevier Inc.",

number = "21-22",

}

TY - JOUR

T1 - Neuroprotective effects of black soybean anthocyanins via inactivation of ASK1-JNK/p38 pathways and mobilization of cellular sialic acids

AU - Kim, Sung Min

AU - Chung, Mi Ja

AU - Ha, Tae Joung

AU - Choi, Ha Na

AU - Jang, Seong Jae

AU - Kim, Sung Oog

AU - Chun, Myung Hoon

AU - Do, Su Il

AU - Choo, Young Kug

AU - Park, Yong Il

N1 - Funding Information: This work was supported by a grant (No. M10619000005-07N1900-00510 ) from the Korea Science and Engineering Foundation (KOSEF) and a grant (No. PJ0071862011 ) from the Cooperative Research Program for Agriculture Science and Technology Development, Rural Development Administration , and partly by a grant from the Next-Generation BioGreen 21 Program (SSAC, PJ008109 ), Rural Development Administration, Republic of Korea.

PY - 2012/6/6

Y1 - 2012/6/6

N2 - Aims: To investigate neuroprotective effects of three major anthocyanins (cyanidin-3-O-glucoside, delphinidin-3-O-glucoside, and petunidin-3-O-glucoside) isolated from the black soybean (Glycine max L.) cv. Cheongja 3 seed coat against H 2O 2-induced cell death of human brain neuroblastoma SK-N-SH cells. Main methods: Cell viability, reactive oxygen species (ROS) generation, production and expression of heme oxygenase (HO)-1 and inactivation of mitogen-activated protein (MAP) kinase cascades were determined by MTT assay, 2,7-dichlorofluorescein diacetate (DCF-DA) assay, reverse transcriptase polymerase chain reaction (RT-PCR), and western blotting, respectively. Key findings: Pretreatment with anthocyanins reduced the cytotoxicity of H 2O 2 on SK-N-SH cells, dose-dependently reduced the intracellular ROS level and inactivated apoptosis signal-regulating kinase (ASK1, Thr845), p38, and c-Jun N-terminal kinase (JNK) proteins. The HO-1 and Neu1 mRNA levels were increased by H 2O 2 (25 μM) and further elevated by the pretreatment with anthocyanins. Sialic acids added to the culture plates not only attenuated the cytotoxicity of H 2O 2 (25 μM) but also reduced intracellular ROS level. These results suggest that Cheongja 3 black soybean seed coat anthocyanins have brain neuroprotective effects against oxidative stress (H 2O 2) by inhibiting the activation of ASK1-JNK/p38 pathways, scavenging ROS, stimulating the expression of HO-1 and, more interestingly, recruiting cellular free sialic acids through up-regulation of Neu1 sialidase gene expression. Significance: This is the first report indicating potent health benefits of black soybean seed coat anthocyanins in neuroprotection by triggering mobilization of cellular free sialic acid and utilizing it as an additional biological antioxidant in brain neural cells.

AB - Aims: To investigate neuroprotective effects of three major anthocyanins (cyanidin-3-O-glucoside, delphinidin-3-O-glucoside, and petunidin-3-O-glucoside) isolated from the black soybean (Glycine max L.) cv. Cheongja 3 seed coat against H 2O 2-induced cell death of human brain neuroblastoma SK-N-SH cells. Main methods: Cell viability, reactive oxygen species (ROS) generation, production and expression of heme oxygenase (HO)-1 and inactivation of mitogen-activated protein (MAP) kinase cascades were determined by MTT assay, 2,7-dichlorofluorescein diacetate (DCF-DA) assay, reverse transcriptase polymerase chain reaction (RT-PCR), and western blotting, respectively. Key findings: Pretreatment with anthocyanins reduced the cytotoxicity of H 2O 2 on SK-N-SH cells, dose-dependently reduced the intracellular ROS level and inactivated apoptosis signal-regulating kinase (ASK1, Thr845), p38, and c-Jun N-terminal kinase (JNK) proteins. The HO-1 and Neu1 mRNA levels were increased by H 2O 2 (25 μM) and further elevated by the pretreatment with anthocyanins. Sialic acids added to the culture plates not only attenuated the cytotoxicity of H 2O 2 (25 μM) but also reduced intracellular ROS level. These results suggest that Cheongja 3 black soybean seed coat anthocyanins have brain neuroprotective effects against oxidative stress (H 2O 2) by inhibiting the activation of ASK1-JNK/p38 pathways, scavenging ROS, stimulating the expression of HO-1 and, more interestingly, recruiting cellular free sialic acids through up-regulation of Neu1 sialidase gene expression. Significance: This is the first report indicating potent health benefits of black soybean seed coat anthocyanins in neuroprotection by triggering mobilization of cellular free sialic acid and utilizing it as an additional biological antioxidant in brain neural cells.

KW - Anthocyanins

KW - H O

KW - Neu1 sialidase

KW - Oxidative stress

KW - Sialic acid

UR - https://www.scopus.com/pages/publications/84861571020

U2 - 10.1016/j.lfs.2012.04.025

DO - 10.1016/j.lfs.2012.04.025

M3 - Article

C2 - 22575822

AN - SCOPUS:84861571020

SN - 0024-3205

VL - 90

SP - 874

EP - 882

JO - Life Sciences

JF - Life Sciences

IS - 21-22

ER -

Neuroprotective effects of black soybean anthocyanins via inactivation of ASK1-JNK/p38 pathways and mobilization of cellular sialic acids

Abstract

Bibliographical note

UN SDGs

Keywords

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